Molecular switch-like regulation enables global subunit coordination in a viral ring ATPase

Proc Natl Acad Sci U S A. 2018 Jul 31;115(31):7961-7966. doi: 10.1073/pnas.1802736115. Epub 2018 Jul 16.

Abstract

Subunits in multimeric ring-shaped motors must coordinate their activities to ensure correct and efficient performance of their mechanical tasks. Here, we study WT and arginine finger mutants of the pentameric bacteriophage φ29 DNA packaging motor. Our results reveal the molecular interactions necessary for the coordination of ADP-ATP exchange and ATP hydrolysis of the motor's biphasic mechanochemical cycle. We show that two distinct regulatory mechanisms determine this coordination. In the first mechanism, the DNA up-regulates a single subunit's catalytic activity, transforming it into a global regulator that initiates the nucleotide exchange phase and the hydrolysis phase. In the second, an arginine finger in each subunit promotes ADP-ATP exchange and ATP hydrolysis of its neighbor. Accordingly, we suggest that the subunits perform the roles described for GDP exchange factors and GTPase-activating proteins observed in small GTPases. We propose that these mechanisms are fundamental to intersubunit coordination and are likely present in other ring ATPases.

Keywords: intersubunit enzymatic regulation; molecular switch-like regulation; ring ATPases; ring-shaped molecular motors; single molecule DNA packaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Diphosphate / chemistry
  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphatases* / chemistry
  • Adenosine Triphosphatases* / metabolism
  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Bacillus Phages / enzymology*
  • Models, Biological*
  • Viral Proteins* / chemistry
  • Viral Proteins* / metabolism

Substances

  • Viral Proteins
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Adenosine Triphosphatases